scholarly journals Zoledronic Acid Enhances the Chemotherapeutic Efficiency of 5-fluorouracil or Flutamide in Prostate Cancer Cells with Modulation of miR-382 and miR-18a Expression

2021 ◽  
Vol 72 (2) ◽  
pp. 102-118
Author(s):  
Amr M. Yehia ◽  
Mahmoud G. Eldeib ◽  
Ahmed M. Mohamadin ◽  
Mohammed M. El-Zahab
Keyword(s):  
Prostate Cancer ◽  
Zoledronic Acid ◽  
Combination Therapy ◽  
Cyclin D1 ◽  
Cancer Cells ◽  
Caspase 3 ◽  
Health Concern ◽  
Prostate Cancer Cells ◽  
Chemotherapeutic Efficacy ◽  
Du145 Cells

Owing to a lack of appropriate therapeutic regimens, prostate cancer (PC) is a global health concern with a high incidence and mortality rate in elderly men. Combination treatment seems to have the highest clinical benefit and avoids unwanted side effects. The current study focused on the chemotherapeutic efficacy of Zoledronic acid (ZA) in combination with 5-fluorouracil (5-FU) or Flutamide on prostate cancer cells, as well as its effect on apoptosis. The MTT assay was used to determine the cytotoxic effect of Zoledronic acid (ZA), 5-FU, and flutamide on PC-3 and DU-145 cells, as well as the combined therapy of ZA with 5-FU or flutamide. Additionally, immunofluorescence staining analysis was used to assess changes in Bcl-2 and p53 expression. Furthermore, the western blotting method was extensively used to evaluate Bax, caspase 3, and cyclin D1. Furthermore, quantitative real-time polymerase chain reaction (qRT-PCR) was applied to determine the relative expression of miRNA-382 (miR-382) and miRNA-18a (miR-18a). Instead of (13.47, 8.23, and 9.42 μM) for PC-3 or (38.77, 17.6, and 8.47 μM) for DU145 cells, the combination therapy improved cytotoxicity with doses approximately half of IC50 (6.74, 4.12, and 7.07 μM) in PC-3 and (19.38, 8.8, and 6.33 μM) in DU145 cells for ZA, 5-FU, and flutamide, respectively. When compared to a single therapy, the combination therapy significantly up-regulated the pro-apoptotic Bax, cleaved caspase 3 and p53 levels while down-regulated the cyclin D1 and Bcl-2 expression. In addition, the combination therapy was linked to changes in miR-382 and miR-18a expression. Our findings suggest that combining ZA with 5-FU or flutamide improves chemotherapeutic efficacy against prostate cancer cells, at least in part by encouraging apoptosis and modulating miRNA expression, especially miR-382 and miR-18a.

scholarly journals Traditional Herbal Formula Taeeumjowi-Tang (TJ001) Inhibits p53-Mutant Prostate Cancer Cells Growth by Activating AMPK-Dependent Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Sooyeon Kang ◽  
Hyo In Kim ◽  
Yu-Jeong Choi ◽  
Seul Ki Lee ◽  
Ji Hye Kim ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Cell Growth ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Caspase 3 ◽  
Mutant P53 ◽  
Prostate Cancer Cells ◽  
Cycle Arrest ◽  
Du145 Cells

Dysregulated lipid metabolism is a prominent feature of prostate cancers (PCas); several enzymes involved in lipid accumulation are highly expressed. Here, we elucidated efficacy of TJ001, a traditional herbal decoction, in inhibiting de novo lipogenesis. TJ001 had significant cytotoxicity against DU145 but not PC3 and LNCaP cells and, similarly, TJ001 markedly AMPK phosphorylation only in DU145 cells. This was accompanied by the downregulation of phosphorylated-acetyl coenzyme A carboxylase (ACC) expression and sterol regulatory element-binding protein 1 (SREBP1) proteolytic cleavage, thereby inhibiting its role as a transcription factor to induce lipid biosynthesis. When Oil Red O staining was performed, it is reflected in the reduction of lipid droplets (LDs). TJ001 also induced G1/S cell cycle arrest via a cell cycle inhibitor (CKI) p21WAF1/CIP1 upregulation. Although p53 proteins remained unchanged, both cyclin E and cyclin D1 were decreased. Moreover, TJ001 suppressed the mammalian target of rapamycin (mTOR) signaling pathway. Generally, the prolonged G1/S phase arrest accompanies apoptosis, but TJ001 failed to work as a trigger apoptosis in DU145 cells. We showed that mutant p53 proteins were required for the survival of DU145 cells. In presence of TJ001, inhibition of endogenous mutant p53 by RNAi led to cell viability reduction and induction of the p-AMPK/AMPK ratio. In addition, it induced apoptotic cell death in DU145 cells. At the cellular level, induction of PARP, caspase-3, and caspase-9 cleavages was observed, and caspase-3 activity was increased in the p53 knockdown cells treated with TJ001. Taken together, we demonstrated that TJ001 inhibited cell growth in DU145 prostate cancer cells as indicated by blocking lipogenesis and induction in G1/S cell cycle arrest. In addition, we may provide an evidence that mutant p53 protein has potential role as an oncogenic action in DU145 cells. Collectively, the combination of mutant p53 targeting and TJ001 treatment resulted in decreased cell growth in DU145 cells.

Cleaved High Molecular Weight Kininogen (HKa) and Kininostatin (D5) Induce Apoptosis and Inhibit Migration and Invasion of Human Prostate Cancer Cells by Preventing AKT Phosphorylation and Cyclin D1 Synthesis and Disrupting the Interaction of UPAR and EGFR.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 405-405
Author(s):  
Yuchuan Liu ◽  
Robin Pixley ◽  
Mario Fusaro ◽  
Robert W. Colman
Keyword(s):  
Prostate Cancer ◽  
Cyclin D1 ◽  
Cancer Cells ◽  
Human Prostate ◽  
Migration And Invasion ◽  
Plasma Kallikrein ◽  
Human Prostate Cancer ◽  
Prostate Cancer Cells ◽  
Du145 Cells

Abstract Tumor metastasis is a major factor in the mortality rate in human prostate cancer. Upregulation and activation of EGFR and/or uPAR in a variety of cancers have been shown to be associated with poor prognosis. HK, a component of the plasma kallikrein-kinin system, can be hydrolyzed by plasma kallikrein to bradykinin and HKa. HKa and D5 both have been demonstrated to have potent anti-angiogenic activity in vitro and in vivo. We previously published that D5 directly inhibits human colon carcinoma cell (HCT-116) proliferation in vitro by blocking the G1/S transition in the cell cycle. We now show that HKa [100 nM] inhibits the migration of human prostate tumor cell (DU145) about 50%. Cyclin D1 can activate p21 and p27 with concomitant cell migration. DU145 cells rapidly increase cyclin D1 synthesis in response to bFGF [1.2 nM]. HKa suppresses cyclin D1 expression as shown by Western blotting as well as cell immunoflourescence. Stimulation by bFGF or VEGF results in clustering of uPAR and EGFR on the surface of DU145 cells. Immunoflourescence shows that the addition of HKa disrupts the co-localization of uPAR and EGFR. HKa or a monoclonal antibody against uPAR decreases the phosphorylation of EGFR at Tyr 1173. The phosphorylation of ERK and AKT, which are downstream effectors of EGFR, is also inhibited by HKa. Kininostatin [300nM] induced apoptosis of human prostate cancer cells challenged with uPA [50 nM] or EGF [6.7 nM]. Matrigel invasion assay reveals that HKa [100 nM] decreases the invading cell number by 90%. These novel data indicate that HKa and kininostatin induce apoptosis and inhibit migration and invasion of human prostate cancer cells, indicating the therapeutic potential of kininostatin in metastasis human prostate cancer.

scholarly journals Cytostatic Action of Novel Histone Deacetylase Inhibitors in Androgen Receptor-Null Prostate Cancer Cells

2021 ◽  
Vol 14 (2) ◽  
pp. 103
Author(s):  
Zohaib Rana ◽  
Joel D. A. Tyndall ◽  
Muhammad Hanif ◽  
Christian G. Hartinger ◽  
Rhonda J. Rosengren
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Cancer Cells ◽  
Hdac Inhibitors ◽  
G1 Arrest ◽  
Prostate Cancer Cells ◽  
Prostate Tumors ◽  
Normal Prostate ◽  
Pc3 Cells ◽  
Du145 Cells

Androgen receptor (AR)-null prostate tumors have been observed in 11–24% of patients. Histone deacetylases (HDACs) are overexpressed in prostate tumors. Therefore, HDAC inhibitors (Jazz90 and Jazz167) were examined in AR-null prostate cancer cell lines (PC3 and DU145). Both Jazz90 and Jazz167 inhibited the growth of PC3 and DU145 cells. Jazz90 and Jazz167 were more active in PC3 cells and DU145 cells in comparison to normal prostate cells (PNT1A) and showed a 2.45- and 1.30-fold selectivity and higher cytotoxicity toward DU145 cells, respectively. Jazz90 and Jazz167 reduced HDAC activity by ~60% at 50 nM in PC3 lysates. At 4 μM, Jazz90 and Jazz167 increased acetylation in PC3 cells by 6- to 8-fold. Flow cytometry studies on the cell phase distribution demonstrated that Jazz90 causes a G0/G1 arrest in AR-null cells, whereas Jazz167 leads to a G0/G1 arrest in DU145 cells. However, apoptosis only occurred at a maximum of 7% of the total cell population following compound treatments in PC3 and DU145 cells. There was a reduction in cyclin D1 and no significant changes in bcl-2 in DU145 and PC3 cells. Overall, the results showed that Jazz90 and Jazz167 function as cytostatic HDAC inhibitors in AR-null prostate cancer cells.

scholarly journals Proteomic analysis of zoledronic-acid resistant prostate cancer cells unveils novel pathways characterizing an invasive phenotype

Oncotarget ◽  
2014 ◽  
Vol 6 (7) ◽  
pp. 5324-5341 ◽  
Author(s):  
Maria Rita Milone ◽  
Biagio Pucci ◽  
Katia Bifulco ◽  
Federica Iannelli ◽  
Rita Lombardi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Zoledronic Acid ◽  
Cancer Cells ◽  
Proteomic Analysis ◽  
Prostate Cancer Cells ◽  
Invasive Phenotype

scholarly journals Hydrogen Sulfide Signaling Axis as a Target for Prostate Cancer Therapeutics

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Mingzhe Liu ◽  
Lingyun Wu ◽  
Sabine Montaut ◽  
Guangdong Yang
Keyword(s):  
Prostate Cancer ◽  
Hydrogen Sulfide ◽  
Cancer Cells ◽  
Current Knowledge ◽  
Cancer Therapeutics ◽  
The Body ◽  
Health Concern ◽  
Diallyl Disulfide ◽  
Castration Resistant Prostate Cancer ◽  
Prostate Cancer Cells

Hydrogen sulfide (H2S) was originally considered toxic at elevated levels; however just in the past decade H2S has been proposed to be an important gasotransmitter with various physiological and pathophysiological roles in the body. H2S can be generated endogenously from L-cysteine by multiple enzymes, including cystathionine gamma-lyase, cystathionine beta-synthase, and 3-mercaptopyruvate sulfurtransferase in combination with cysteine aminotransferase. Prostate cancer is a major health concern and no effective treatment for prostate cancers is available. H2S has been shown to inhibit cell survival of androgen-independent, androgen-dependent, and antiandrogen-resistant prostate cancer cells through different mechanisms. Various H2S-releasing compounds, including sulfide salts, diallyl disulfide, diallyl trisulfide, sulforaphane, and other polysulfides, also have been shown to inhibit prostate cancer growth and metastasis. The expression of H2S-producing enzyme was reduced in both human prostate cancer tissues and prostate cancer cells. Androgen receptor (AR) signaling is indispensable for the development of castration resistant prostate cancer, and H2S was shown to inhibit AR transactivation and contributes to antiandrogen-resistant status. In this review, we summarized the current knowledge of H2S signaling in prostate cancer and described the molecular alterations, which may bring this gasotransmitter into the clinic in the near future for developing novel pharmacological and therapeutic interventions for prostate cancer.

Sign in / Sign up

Export Citation Format

Share Document